The proposed project is designed to investigate the organization of central nervous system pathways involved in cardiac regulation. In the first part, a retrograde axonal transport double-label method using different colored fluorescent dyes will be used to identify neurons which have specific projections to the second through sixth thoracic spinal segments, in which most cardiac sympathetic preganglionic neurons are found. In the second part, the autoradiographic anterograde axonal transport method will be used to distinguish which of the cell groups with specific T2-T6 projections actually innervate the sympathetic preganglionic neurons at those levels. In the third part, both the autoradiographic anterograde method and the retrograde transport of wheat germ agglutinin-conjugated-horseradish peroxidase will be used to trace the afferent and efferent connections of cell groups which innervate the T2-T6 preganglionic neurons. These experiments will provide a detailed map of potential central cardiac connections for later physiological, immunohistochemical and pharmacological studies. Such information will be critical in delineating the mechanisms by which the central cardiac system interacts with other neuronal systems such as those concerned with behavioral and neuroendocrine regulation, and in the design of rational therapies at the central nervous system level for myocardial ischemia and cardiac arrhythmias.